PROGRAM 3: Integration of homeostatic and dynamic signals: genotoxic stress responses. Eukaryotic organisms have evolved multiple mechanisms of sensing DNA damage and genotoxic stress. The resulting signals are integrated though a regulatory network that also samples the metabolic health of the cell by involving mitochondrial signaling mediators. By integrating dynamic genotoxic response signals and homeostatic regulatory networks, cells determine a variety of different responses, including the decision to undergo cell death via apoptotic or necroptotic pathways. In this Program, we will employ a systems approach to elucidating the mitochondria-dependent cell death program that is conserved from yeast to mammalian cells.